The legal cannabis movement started in San Francisco in the early 1990’s when it was discovered that cannabis treated many symptoms that AIDS patients suffered from, including pain. It was medical marijuana laws that changed the legal status of cannabis nationwide, opening the doors for an adult-use market and creating a path towards full legalization. Cannabis patients across the country have used the plant to treat a growing number of medical conditions. In Colorado alone, there are nine different qualifying conditions for a medical card: cancer, glaucoma, HIV or AIDS, cachexia (wasting syndrome), persistent muscle spasms, seizures, severe nausea, severe pain, and Post Traumatic Stress Disorder (PTSD). How does cannabis address so many different conditions? How does the body interact with the plant to produce these medicinal effects? What research has been to done to demonstrate the efficacy of medicinal cannabis?
To dive into these questions, it’s crucial to have a basic understanding of the endogenous cannabinoid system, otherwise known as the endocannabinoid system (ECS). The endocannabinoid system is essential to human health because it maintains homeostasis in the body. Research into the endocannabinoid system has increased in recent years as scientists begin to reveal how complex and important this system is to our bodies. By understanding the endocannabinoid system and how it interacts with cannabis, patients and consumers can become more informed about their health and can ask their caregivers, doctors, or budtenders better questions.

What is the endocannabinoid system?

Put simply, the endocannabinoid system is responsible for maintaining homeostasis in the body. The Encyclopedia Britannica definition of homeostasis is, “any self-regulating process by which biological systems tend to maintain stability while adjusting to conditions that are optimal for survival. If homeostasis is successful, life continues; if unsuccessful, disaster or death ensues.”The endocannabinoid system is made up of three parts: cannabinoid receptors, endocannabinoids, and metabolic enzymes.
Endocannabinoid receptors are found throughout the body on the surface of cells in the brain, organs, tissues, and glands. These receptors are embedded in cell membranes and produce varying reactions when stimulated by cannabinoids. Cannabinoids come from two distinct places — the body, which produces naturally occurring endocannabinoids, and the cannabis plant, which produces phytocannabinoids. The third part of the ECS is metabolic enzymes. Metabolic enzymes act like a natural referee in that they destroy endocannabinoids once they are used and no longer useful to the body. The two main metabolic enzymes are fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). This self-regulating system ensures the interaction only happens when needed and therefore keeps the workings of the endocannabinoid system relatively quiet to the conscious brain, unlike, the hormonal system, which can keep the chemicals around longer than the interaction. Because homeostasis is so important to health, all vertebrates and invertebrates are known to have an ECS.
Dr. Ethan Russo, a neurologist and psychopharmacology researcher, breaks down the ECS this way, “the endocannabinoid system affects the levels of all the neurotransmitters, and so it is important in pain, in emotion, whether you’re going to vomit or not, whether you’re going to have a seizure or not, almost any function you can name, and it’s not just the brain.”

The Endocannabinoid System

Research and discovery

Despite its critical importance, the endocannabinoid system was only discovered in the early 1990s when Lisa Matsuda, a researcher at the National Institute of Mental Health, and her colleagues discovered a DNA sequence that defines a THC-sensitive receptor in a rat’s brain. This discovery was quickly followed up with further evidence by Dr. Raphael Mechoulam, the famous chemist who discovered THC. With less than 30 years of research, the endocannabinoid system is one of the less studied systems in the body. Currently, restrictions on cannabis research limit what scientists can examine in terms of furthering our understanding of how cannabis interacts with the endocannabinoid system.

Dr. Ethan Russo states, “if we look at any aspect of how our bodies work, our physiology, you’ve got some element of the endocannabinoid system that affects that. So it is a key modulator of what we call homeostasis, that’s a natural balance in the body. When someone uses cannabis medicinally they are keying into these natural mechanisms which sometimes are deficient and need supplementation.”

Cannabinoid receptors

Cannabinoid receptorsSo what do we know about how cannabis interacts with our bodies and the endocannabinoid system? Two cannabinoid receptors have been discovered by researchers: CB1 and CB2. CB1 is found in the central and peripheral nervous system. It’s also found in the brain and is the receptor that THC interacts with, giving the user a high. CB2 receptors are predominantly found in the immune system and the gastrointestinal system where they regulate inflammatory responses in the bowels. CB2 receptors are also found in the brain, although not as densely as CB1 receptors. These receptors, a large part of the endocannabinoid system, play roles in regulating cardiovascular activity, appetite, mood, memory, and pain in the body.

CBD and the endocannabinoid system

CBD does not fit exactly into either CB1 or CB2 receptors. CBD stimulates both receptors and causes a reaction without binding directly, creating changes in cells that contain them. CBD also binds to a protein-receptor couple, TRPV-1, responsible for regulating body temperature, pain, and inflammation. CBD is also known for counteracting the effects of THC, activating serotonin receptors, and inhibiting a gene attributed to several cancers. CBD has grown in popularity recently as research and anecdotal evidence increasingly demonstrates the impact it can have on the body. Julianna Carella, the Founder & CEO of two edible companies, Auntie Dolores and Treatibles, states, “if you haven’t acknowledged that the endocannabinoid system exists, then it’s very easy to dispute the purported results that people and animals get from CBD because how can this possibly work so profoundly. Well, it works very profoundly because apparently, we’re set up to need this in our systems.”

Where do cannabinoids come from?

Cannabinoids generally come from two places — the human body or the cannabis plant. However, there is a third place that is important to consider, a lab. Cannabinoids can be produced synthetically and distributed on the market. Marinol (dronabinol) and Cesamet (nabilone) are synthetic versions of THC that have FDA approval to be marketed and sold as a prescription drug. Synthetic cannabinoids do bind the endocannabinoid system to produce effects, but they often fail to incorporate one of the most important ideas in the medical cannabis community, the entourage effect. The entourage effect states that the sum of the different cannabinoids works better as a whole unit than any cannabinoid individually. With an understanding of the endocannabinoid system and its role in ensuring homeostasis in the body, it may be easier to see how this could be true.

The endocannabinoid system and health

The endocannabinoid system is a huge part of the human body that we are just beginning to understand. Carella states, “it’s largely overlooked in the medical community. It’s not taught in medical schools. It’s definitely not taught in veterinary schools. So doctors and veterinarians are essentially misguided around a huge, huge piece of science that has been sort of strategically removed from the consciousness and unfortunately it means that we’re quite behind with our research, but there’s enough research out there for us to know that indeed all animals have an endocannabinoid system and that this endocannabinoid system is actually incredibly important in our physiology.” The American Medical Association and the American College of Physicians are calling for more research into medical cannabis and its impact on humans. Until then, it’s important, especially for patients and consumers, to stay informed about the endocannabinoid system and the evolving science of medical cannabis. Learn more about the endocannabinoid system at Wikipedia.